Keep amyloid away from neurons
A drug has been found that can defeat Alzheimer's disease
Dmitry Mazalevsky, Naked Science
One of the main features of debilitating Alzheimer's disease, which is characterized by cognitive impairment, is the accumulation in the brain of a protein called beta–amyloid. It forms a kind of plaques and binds to unique proteins on the surface of brain cells, which leads to mass cell death.
A group of scientists led by Dr. Lin Jiang and Professor of biochemistry David Eisenberg from the University of California Los Angeles has discovered a drug that prevents the attachment of these plaques to brain cells, preventing extensive cell death. Scientists were able to identify the binding site of beta-amyloid plaques to the LilrB2 receptor by determining its three-dimensional structure. This was a significant step in the search for a drug to prevent the interaction between toxic proteins and brain cells. The study was published in the journal Nature Chemistry (Cao et al., Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design).
"We were looking for a molecule that could, like a shield, block the receptor, preventing beta-amyloid binding to brain cells, protecting them from death," says Jiang (in a press release UCLA Researchers discover drug that could combat brain cell death in those with Alzheimer's disease – VM).
To find the right molecule, Jiang and his colleagues studied a database containing more than 32 thousand molecules. This list includes both drugs that are safe for humans, and those that are still undergoing clinical trials or simply found in nature. This meant that many of the characteristics of the potential molecule are already known, which means they are safe for the human body. From this extensive list, the drug ALI6 was isolated, which showed promising results.
Experts exposed mouse brain cells to toxic beta-amyloid proteins, and then treated some of them with ALI6 and compared the number of dead cells. ALI6 almost completely prevented the cell death caused by beta-amyloid, which indicates that the drug can be used to treat Alzheimer's disease.
Scientists call ALI6 a promising candidate. Firstly, it is non-toxic, and secondly, it is able to pass from the bloodstream to the brain: this is a critical sign for any drug intended for the treatment of disorders of the central nervous system, such as Alzheimer's disease.
"Currently, many drugs are aimed at preventing the accumulation and transformation of beta-amyloid proteins into plaques. However, when a person is diagnosed with Alzheimer's disease, many beta-amyloid plaques have already formed, so there is no possibility of treatment," says the scientist.
Alzheimer's disease is the sixth leading cause of death in the United States, where 5.7 million people are currently living with this disease.
Scientists emphasize that the results of the study must first be confirmed during further animal trials before the drug is tested on humans.
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